OP0253 REAL-WORLD DEMOGRAPHICS, CLINICAL CHARACTERISTICS, AND TREATMENT PATTERNS OF PATIENTS TREATED WITH EMAPALUMAB FOR SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN THE UNITED STATES: THE REAL-HLH STUDY
Authors: C. Allen, S. Chandrakasan, M. Jordan, J. Leiding, A. Oladapo, P. Pednekar, K. Walkovich, J. Yee
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome caused by overproduction of proinflammatory cytokines, e.g., interferon gamma (IFNγ).[1,2] Secondary HLH (sHLH) occurs in the context of an underlying disease (e.g., rheumatologic, malignancy, or iatrogenic) and/or an infectious trigger.[1,2] Emapalumab is a fully human anti-IFNγ monoclonal antibody that binds to and neutralizes the biological activity of IFNγ. It was approved by the FDA in 2018 for adults and children with primary HLH with refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy. Since its approval, real-world evidence on the use of emapalumab in routine clinical setting is limited.[3-5] The REAL-HLH study assessed real-world treatment patterns among patients treated with emapalumab. <h3>Objectives</h3> To describe the demographics, clinical characteristics, and treatment patterns among the subset of patients with physician-reported diagnosis of sHLH treated with emapalumab. <h3>Methods</h3> A retrospective medical chart review conducted across 33 US hospitals identified patients treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data on the subset of patients with sHLH extracted from time of emapalumab initiation to end of data availability, death, or study end (December 31, 2021) are presented. <h3>Results</h3> Overall, 57/105 (54.3%) enrolled patients had a physician-reported diagnosis of sHLH (mean age [± SD] 10.4 [7.6] years). Majority of patients were non-White (63.2%) and male (52.6%). At diagnosis, mean age (±SD) was 9.3 (7.5) years and 15/17 (88.2%) patients with available data met ≥5 of 8 HLH-2004 diagnostic criteria. Underlying disease and/or triggers were identified in 53/57 (92.9%) patients; 22/53 (41.5%) had a single trigger and 31/53 (58.5%) had multiple triggers. Infections (32/53; 60.4%), malignancy (18/53; 34%), rheumatologic disease (11/53; 20.8%), and iatrogenic (6/53; 11.3%) were the most common triggers. Epstein-Barr virus (11/25; 44%) was the most common viral (25/32; 78.1%) infection. At time of emapalumab initiation, 73.7% of patients had received prior treatments with other HLH-related therapies, including corticosteroids, and 62.5% of patients were in the intensive care unit. Emapalumab was mainly initiated for treatment of refractory (42.1%), progressive (29.8%), and recurrent (14%) disease. The median (range) time to emapalumab initiation from diagnosis was 16.5 (1-2278) days. Median (range) treatment duration with emapalumab was 38.0 (1-397) days. Median (range) emapalumab starting dose was 1.1 (0.7-5.9) mg/kg and cumulative treatment dose was 21.3 (1-336.5) mg/kg. Median (range) maximum administered emapalumab dose was 2.3 (0.7-12.5) mg/kg. <h3>Conclusion</h3> This is the first study to report real-world treatment patterns with emapalumab across a diverse patient population with sHLH. A pivotal clinical trial of emapalumab in patients with sHLH and underlying rheumatologic disease is ongoing (NCT05001737). <h3>References</h3> [1]Allen CE, McClain KL. <i>Hematology Am Soc Hematol Educ Program</i>. 2015;2015:177-182. [2]Jordan MB, et al. <i>Blood</i>. 2011;118:4041-4052. [3]Hatterer E, et al. <i>Cytokine</i>. 2012;59:570. [4]US Food and Drug Administration. https://www.fda.gov/drugs/fda-approves-emapalumab-hemophagocytic-lymphohistiocytosis. Accessed August 2, 2022. [5]Locatelli F, et al. <i>N Engl J Med</i>. 2020;382:1811-1822. <h3>Acknowledgements</h3> The authors thank Sajjad Raza and Alice Pressman (PRECISIONheor) and Corey Best (Sobi, Inc) for their support. Editorial and medical writing support was provided by Sonali K. Kalra, PhD, of rareLife solutions, Westport, CT, USA, and funded by Sobi, Inc. <h3>Disclosure of Interests</h3> Carl Allen Consultant of: Sobi, Inc., Shanmuganathan Chandrakasan Consultant of: Sobi, Inc., Michael Jordan Consultant of: Sobi, Inc., Jennifer Leiding Consultant of: Sobi, Inc., Employee of: bluebird bio, Abiola Oladapo Employee of: Sobi, Inc., Priti Pednekar Consultant of: Sobi, Inc., Kelly Walkovich Consultant of: Sobi, Inc., John Yee Employee of: Sobi, Inc.